Maternal Deprivation Enhances Contextual Fear Memory via Epigenetically Programming Second-Hit Stress-Induced Reelin Expression in Adult Rats
Abstract
Early-life stress increases the risk for posttraumatic stress disorder. However, the epigenetic mechanism of early-life stress-induced susceptibility to posttraumatic stress disorder in adulthood remains unclear. Rat pups were exposed to maternal deprivation during postnatal days 1 to 14 for 3 hours daily and treated with the DNA methyltransferase inhibitor zebularine, L-methionine, or vehicle 7 days before contextual fear conditioning, which was used as a second stress and to mimic the reexperiencing symptom of posttraumatic stress disorder in adulthood. Long-term potentiation, dendritic spine density, DNA methyltransferase mRNA, Reelin gene methylation, and Reelin protein expression in the hippocampal CA1 were measured. Maternal deprivation enhanced contextual fear memory in adulthood. Meanwhile, maternal deprivation decreased DNA methyltransferase mRNA and Reelin gene methylation in the hippocampal CA1 on postnatal days 22 and 90. Reelin protein expression was increased in the hippocampal CA1 following contextual fear conditioning in adulthood. Furthermore, compared with rats that experienced maternal deprivation alone, rats also exposed to contextual fear conditioning showed an enhanced induction of hippocampal long-term po...Continue Reading
References
The maternal separation paradigm and adult emotionality and cognition in male and female Wistar rats
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